Natural history and clinical significance of MRI-detected bone marrow lesions at the knee: a prospective study in community dwelling older adults

Introduction  

There are conflicting data on the natural history and clinical significance of bone marrow lesions (BMLs). The aims of this study were to describe the natural history of MRI-detected BMLs at the knee using a quantitative measure and examine the association of BMLs with pain, function and stiffness scores, and total knee replacement (TKR) surgery.     

Xerostomia in older adults: a longitudinal study

Although xerostomia in older adults has received substantial research attention, there have been few longitudinal studies of non-patient populations. Consequently, little is known about the incidence or course of this condition among this group. This paper reports the results of a longitudinal study designed to address these issues. In 1989, data on xerostomia were collected from 907 randomly-selected community dwelling adults aged 50 years and over. Three years later, 611 (71% of those presumed to be alive) were followed-up and data on xerostomia collected again. At baseline, 15.5% of these 611 subjects reported xerostomia, while at follow-up this had risen to 29.5%. The majority of the latter (115/180) were incident cases, reporting xerostomia only at follow-up, while the remainder were chronic cases, reporting xerostomia at both baseline and follow-up. A crude estimate of the three-year incidence rate was 22.5%. In a logistic regression analysis, three baseline variables were associated with incidence; older subjects, those with one or more chronic medical conditions and those reporting their general health as poor were more likely to develop xerostomia. In a similar analysis, age was the only variable associated with chronicity, with older subjects more likely to be chronic cases. The data also suggest that the onset of xerostomia was associated with an increase in other oral symptoms and problems with eating, communication and social interaction.     

Characterizing upper limb muscle volume and strength in older adults: a comparison with young adults

Aging is associated with the loss of muscle volume (MV) and force leading to difficulties with activities of daily living. However, the relationship between upper limb MV and joint strength has not been characterized for older adults. Quantifying this relationship may help our understanding of the functional declines of the upper limb that older adults experience. Our objective was to assess the relationship between upper limb MV and maximal isometric joint moment-generating capacity (IJM) in a single cohort of healthy older adults (age ≥ 65 years) for 6 major functional groups (32 muscles). MV was determined from MRI for 18 participants (75.1±4.3 years). IJM at the shoulder (abduction/adduction), elbow (flexion/extension), and wrist (flexion/extension) was measured. MV and IJM measurements were compared to previous reports for young adults (28.6±4.5 years). On average older adults had 16.5% less total upper limb MV compared to young adults. Additionally, older adult wrist extensors composed a significantly increased percentage of upper limb MV. Older adult IJM was reduced across all joints, with significant differences for shoulder abductors (p<0.0001), adductors (p=0.01), and wrist flexors (p<0.0001). Young adults were strongest at the shoulder, which was not the case for older adults. In older adults, 40.6% of the variation in IJM was accounted for by MV changes (p≤0.027), compared to 81.0% in young adults. We conclude that for older adults, MV and IJM are, on average, reduced but the significant linear relationship between MV and IJM is maintained. These results suggest that older adult MV and IJM cannot be simply scaled from young adults.     

Dietary fatty acid intake affects the risk of developing bone marrow lesions in healthy middle-aged adults without clinical knee osteoarthritis: a prospective cohort study

Introduction  

Fatty acids have been implicated in osteoarthritis (OA), yet the mechanism by which fatty acids affect knee structure and consequently the risk of knee OA has not been fully elucidated. Higher intakes of fatty acids have been shown to be associated with the risk of bone marrow lesions (BMLs) in a healthy population. The aim of this study was to examine the association between fatty acid consumption and the incidence of BMLs in healthy middle-aged adults without clinical knee OA.     

Aerobic exercise and its impact on musculoskeletal pain in older adults: a 14 year prospective,longitudinal study

We studied the long term impact of running and other aerobic exercise on musculoskeletal pain in a cohort of healthy aging male and female seniors who had been followed for 14 years. We conducted a prospective, longitudinal study in 866 Runners' Association members (n = 492) and community controls (n = 374). Subjects were also categorized as Ever-Runners (n = 565) and Never-Runners (n = 301) to include runners who had stopped running. Pain was the primary outcome measure and was assessed in annual surveys on a double-anchored visual analogue scale (0 to 100; 0 = no pain). Baseline differences between Runners' Association members and community controls and between Ever-Runners versus Never-Runners were compared using chi-square and t-tests. Statistical adjustments for age, body mass index (BMI), gender, health behaviors, history of arthritis and comorbid conditions were performed using generalized estimating equations. Runner's Association members were younger (62 versus 65 years, p < 0.05), had a lower BMI (22.9 versus 24.2, p < 0.05), and less arthritis (35% versus 41%, p > 0.05) than community controls. Runners' Association members averaged far more exercise minutes per week (314 versus 123, p < 0.05) and miles run per week (26 versus 2, p < 0.05) and tended to report more fractures (53% versus 47%, p > 0.05) than controls. Ever-Runners were younger (62 versus 66 years, p < 0.05), had lower BMI (23.0 versus 24.3, p < 0.05), and less arthritis (35% versus 43%, p < 0.05) than Never-Runners. Ever-Runners averaged more exercise minutes per week (291 versus 120, p < 0.05) and miles run per week (23 versus 1, p < 0.05) and reported a few more fractures (52% versus 48%, p > 0.05) than Never-Runners. Exercise was associated with significantly lower pain scores over time in the Runners' Association group after adjusting for gender, baseline BMI, and study attrition (p < 0.01). Similar differences were observed for Ever-Runners versus Never-Runners. Consistent exercise patterns over the long term in physically active seniors are associated with about 25% less musculoskeletal pain than reported by more sedentary controls, either by calendar year or by cumulative area-under-the-curve pain over average ages of 62 to 76 years.     

Executive function and falls in older adults: new findings from a five-year prospective study link fall risk to cognition

BACKGROUND: Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. METHODOLOGY/MAIN RESULTS: We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74-.98, p?=?.021), the attention index (RR: .84; CI: .75-.94, p?=?.002) and dual tasking gait variability (RR: 1.11; CI: 1.01-1.23; p?=?.027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.     

Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study

Introduction  

Given the emerging evidence that osteoarthritis (OA) may have a vascular basis, the aim of this study was to determine whether serum lipids were associated with change in knee cartilage, presence of bone marrow lesions (BMLs) at baseline and the development of new BMLs over a 2-year period in a population of pain-free women in mid-life.     

Knee meniscal extrusion in a largely non-osteoarthritic cohort: association with greater loss of cartilage volume

We conducted a longitudinal study (duration 2 years), including 294 individuals (mean age 45 years, 58% female), in order to examine associations between meniscal extrusion, knee structure, radiographic changes and risk factors for osteoarthritis (OA) in a largely non-osteoarthritic cohort. Meniscal extrusion, tibiofemoral cartilage defect score and cartilage volume, and tibial plateau bone area were determined using T1-weighted fat-saturated magnetic resonance imaging. At baseline the presence of medial meniscal extrusion was significantly associated with body mass index (odds ratio [OR] per kg/m2 = 1.13, 95% confidence interval [CI] = 1.02-1.25), past knee injury (positive versus negative history: OR = 3.73, 95% CI = 1.16-11.97), medial tibial bone area (OR per cm2 = 1.37, 95% CI = 1.02-1.85), and osteophytes (OR per grade = 4.89, 95% CI = 1.59-15.02). Two-year longitudinal data revealed that medial meniscal extrusion at baseline was associated with a greater rate of loss of medial tibiofemoral cartilage volume (extrusion versus no extrusion: -1.4%/year; P < 0.05) and greater risk for increased medial femoral cartilage defects (OR = 2.59, 95% CI = 1.14-5.86) and lateral tibial cartilage defects (OR = 2.64, 95% CI = 1.03-6.76). However, the latter two associations became nonsignificant after adjustment for tibial bone area and osteophytes. This study suggests that increasing body mass index and bone size, past knee injury, and osteophytes may be causally related to meniscal extrusion. Most importantly, meniscal extrusion at baseline is associated with greater loss of knee cartilage over 2 years, and this seems to be mediated mostly by subchondral bone changes, suggesting extrusion represents one pathway between bone expansion and cartilage loss.     

Bone marrow and thymus regeneration is a condition for thymoma development

Degeneration and regeneration of bone marrow was measured by nucleated cell number changes and of thymus and spleen by weight changes in adult female inbred SwisS mice given a single sub-lethal dose of methyl methanesulphonate (MMS), ethyl methanesulphonate (EMS), N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), or N-ethyl-N-nitrosourea (ENUA).Significant cell number decreases of the bone marrow were observed only following ENUA, the only one of the four agents capable of enhancing thymoma development in these mice. ENUA also caused the greatest significant weight decrease of the thymus and the spleen. Return to normal occurred before the 20th day of the experiment.It is suggested that bone marrow and thymus regeneration is an essential step in thymoma development.     

Tooth loss and dental caries in community-dwelling older adults in northern Manhattan

doi: 10.1111/j.1741‐2358.2011.00502.x Tooth loss and dental caries in community‐dwelling older adults in northern Manhattan Objective: To examine tooth loss and dental caries by sociodemographic characteristics from community‐based oral health examinations conducted by dentists in northern Manhattan. Background: The ElderSmile programme of the Columbia University College of Dental Medicine serves older adults with varying functional capacities across settings. This report is focused on relatively mobile, socially engaged participants who live in the impoverished communities of Harlem and Washington Heights/Inwood in northern Manhattan, New York City. Materials and Methods: Self‐reported sociodemographic characteristics and health and health care information were provided by community‐dwelling ElderSmile participants aged 65 years and older who took part in community‐based oral health education and completed a screening questionnaire. Oral health examinations were conducted by trained dentists in partnering prevention centres among ElderSmile participants who agreed to be clinically screened (90.8%). Results: The dental caries experience of ElderSmile participants varied significantly by sociodemographic predictors and smoking history. After adjustment in a multivariable logistic regression model, older age, non‐Hispanic Black and Hispanic race/ethnicity, and a history of current or former smoking were important predictors of edentulism. Conclusion: Provision of oral health screenings in community‐based settings may result in opportunities to intervene before oral disease is severe, leading to improved oral health for older adults.     

Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study

Background

The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO₂) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO₂ and mortality in oxygen-dependent COPD.

Methods

National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO₂ while breathing air, PaCO₂ (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO₂), World Health Organization performance status, body mass index, comorbidity, and medications.

Results

Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO₂ (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO₂ (air) 6.5 kPa and increased mortality at PaCO₂ (air) below 5.0 kPa and above 7.0 kPa.

Conclusion

In oxygen-dependent COPD, PaCO₂ (air) is an independent prognostic factor with a U-shaped association with mortality.     

Chewing disability in older adults attributable to tooth loss and other oral conditions

doi: 10.1111/j.1741‐2358.2010.00412.x Chewing disability in older adults attributable to tooth loss and other oral conditions Background: This study evaluates associations between oral health‐related factors and chewing ability, and quantifies the risk contributed by each factor. Materials and methods: Chewing ability and information on number of teeth, dentures and dental problems over the last 12 months were collected by mailing questionnaires to a random sample of 60‐ to 71‐year‐olds from Adelaide, South Australia. Logistic regression was used to model oral status and oral symptoms as predictors of chewing disability, and to estimate the population‐attributable fraction. Results: A total of 444 persons responded (response rate = 68.8%). Among dentate subjects, 10.3% were chewing‐deficient, with chewing disability more prevalent (p < 0.05) among those with <21 teeth (26.4%), dentures (20.4%), painful aching in the mouth (25.4%), pain in the face (16.7%), broken/chipped teeth (15.6%), sensitive teeth (14.1%), loose teeth (37.1%), and sore gums (18.0%). Adjusted Odds ratios (OR) showed inadequate dentition (OR = 4.20), painful aching in the mouth (OR = 4.88), and presence of loose teeth (OR = 4.70) were associated with chewing disability (p < 0.01), and their population attributable fractions were 18.5%, 15.1% and 7.8% respectively. Conclusions: Loose teeth, number of teeth and pain in the mouth were associated with chewing disability, with an inadequate dentition and pain in the mouth contributing most to chewing disability in this population.     

MRI osteitis predicts cartilage damage at the wrist in RA: a three-year prospective 3T MRI study examining cartilage damage

Introduction

Cartilage damage impacts on patient disability in rheumatoid arthritis (RA). The aims of this magnetic resonance imaging (MRI) study were to investigate cartilage damage over three years and determine predictive factors.

Methods

A total of 38 RA patients and 22 controls were enrolled at t = 0 (2009). After 3 years, clinical and MRI data were available in 28 patients and 15 controls. 3T MRI scans were scored for cartilage damage, bone erosion, synovitis and osteitis. A model was developed to predict cartilage damage from baseline parameters.

Results

Inter-reader reliability for the Auckland MRI cartilage score (AMRICS) was high for status scores; intraclass correlation coefficient (ICC), 0.90 (0.81 to 0.95) and moderate for change scores (ICC 0.58 (0.24 to 0.77)). AMRICS scores correlated with the Outcome MEasures in Rheumatoid Arthritis Clinical Trials (OMERACT) MRI joint space narrowing (jsn) and X-Ray (XR) jsn scores (r =0.96, P < 0.0001 and 0.80, P < 0.0001, respectively). AMRICS change scores were greater for RA patients than controls (P = 0.06 and P = 0.04 for the two readers). Using linear regression, baseline MRI cartilage, synovitis and osteitis scores predicted the three-year AMRICS (R² = 0.67, 0.37 and 0.39, respectively). A multiple linear regression model predicted the three-year AMRICS (R² = 0.78). Baseline radial osteitis predicted increased cartilage scores at the radiolunate and radioscaphoid joints, P = 0.0001 and 0.0012, respectively and synovitis at radioulnar, radiocarpal and intercarpal-carpometacarpal joints also influenced three-year cartilage scores (P-values of 0.001, 0.04 and 0.01, respectively).

Conclusions

MRI cartilage damage progression is preceded by osteitis and synovitis but is most influenced by pre-existing cartilage damage suggesting primacy of the cartilage damage pathway in certain patients.     

Incidence of asthma and mortality in a cohort of young adults: a 7-year prospective study

Background

CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology.

Methods

The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system.

Results

We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis.

Conclusions

Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology.     

Contractile and non-contractile tissue volume and distribution in ankle muscles of young and older adults

Magnetic resonance imaging (MRI) enables accurate in vivo quantification of human muscle volumes, which can be used to estimate subject-specific muscle force capabilities. An important consideration is the amount of contractile and non-contractile tissue in the muscle compartment, which will influence force capability. We quantified age-related differences in the proportion and distribution of contractile and non-contractile tissue in the dorsiflexor and plantar flexor (soleus, and medial and lateral heads of gastrocnemius) muscles, and examined how well these volumes can be estimated from single MRI cross-sections. Axial MRIs of the left leg for 12 young (mean age 27 years) and 12 older (72 years) healthy, active adults were used to compute muscle volumes. Contractile tissue distribution along the leg was characterized by mathematical functions to allow volume prediction from single-slice cross-sectional area (CSA) measurements. Compared to young, older adults had less contractile volume and a greater proportion of non-contractile tissue. In both age groups the proportion of non-contractile tissue increased distally, with the smallest proportion near the maximum compartment CSA. A single CSA measurement predicted contractile volume with 8-11% error, with older adults in the higher end of this range. Using multiple slices improved volume estimates by roughly 50%, with average errors of about 3-4%. These results demonstrate significant age-related differences in non-contractile tissue for the dorsi- and plantar-flexor muscles. Although estimates of contractile volume can be obtained from single CSA measurements, multiple slices are needed for increased accuracy due to inter-individual variations in muscle volume and composition.